2 History of Endothelial Keratoplasty Although the idea of lamellar keratoplasty was introduced 200 years ago, for a long time these techniques were perceived as too complicated to be adopted by contemporary surgeons. After Dr. Eduard Zirm performed the first successful penetrating keratoplasty (PK) in 1905,1 the full-thickness technique remained the only available treatment for corneal disorders for almost a century. Thus, in eyes with corneal endothelial disease, not only the diseased cell layer but also healthy layers of the cornea were replaced by a full-thickness penetrating transplant. This also remained the status quo after another attempt was made in the 1950s by Dr. José Barraquer and Dr. Charles Tillett, who introduced the concept of lamellar keratoplasty into clinical practice. They performed the first posterior lamellar endothelial transplant underneath a manually dissected stromal flap that was secured by sutures.2,3,4 However, the lack of adequate instruments to create thin corneal layers and limited knowledge of endothelial cell physiology resulted in early complications and insufficient functional results5 that brought further developments of these techniques to a halt. Although in the early 1990s various scientists continued to evaluate the replacement of posterior corneal tissue underneath a sutured stromal flap in experimental animal models,6 describing a sclerocorneal approach,7 or trying to standardize flap preparation by using a microkeratome,8 it was only in 1998 that the first clinically successful case of endothelial keratoplasty (EK) was presented. At that time, PK was still considered the standard of care for unselective treatment of all diseased corneal layers. However, well-known and profound intra- and postoperative complications of this technique could not be sufficiently solved in the past 100 years and still 30 to 50% of indications for PK affected solely the corneal endothelium,9 resulting in the unnecessary replacement of healthy anterior corneal tissue in treating corneal endothelial disorders. These facts were probably the reason for the following rapid advances and the breakthrough of EK in the following years. The first encouraging successful steps in EK led to refinements that transformed the technique into a less invasive procedure, with thinner transplants, while extinguishing many complications associated with PK and obtaining unexpected and unprecedented clinical outcomes (► Fig. 2.1).10 In 1998, Melles and colleagues introduced the first successful approach for posterior lamellar keratoplasty (PLK) in humans, in which an unsutured donor posterior corneal disc, consisting of posterior stroma, Descemet membrane, and endothelium, was transplanted into the anterior chamber through a limbal incision.11,12 In 2001, this technique was popularized as deep lamellar endothelial keratoplasty (DLEK) in the United States by Terry and Ousley.13 This PLK/DLEK technique consisted of a posterior lamellar disc dissected from the recipient cornea through a 9 mm sclerocorneal incision and replaced by an equally sized donor disc. The latter was introduced into the recipient anterior chamber and placed against the recipient posterior cornea secured only by an air bubble, while the patient had to remain in a supine position.14 In 2000, Melles et al improved the technique by creating a smaller, self-sealing, 5 mm tunnel incision through which the **taco-folded** donor (endothelium, Descemet membrane, and a layer of stroma) was inserted, and then unfolded inside the recipient anterior chamber.15 This less invasive technique, popularized as **small incision** DLEK, soon proved to provide clinical outcomes surpassing PK while diminishing many PK-associated complications,16,17,18 but it was still challenging regarding donor and host tissue manual dissection. In 2002, Melles et al further simplified the concept of EK by introducing a technique that facilitated selective removal (**stripping**) of the host diseased corneal Descemet membrane and its endothelium using a reversed Sinskey hook. This step, known as descemetorhexis, was then followed by the insertion of a taco-folded posterior lamellar disc, similar to the one used in PLK/DLEK, which was then positioned onto the denuded host posterior stroma.19 Price and colleagues later popularized this technique as Descemet stripping endothelial keratoplasty (DSEK).20,21 At the same time Gorovoy and colleagues facilitated donor preparation by means of an automated microkeratome that enabled standardized dissection of the donor posterior lamella from a corneoscleral button while mounted on an artificial anterior chamber; to differentiate this technique from manually dissected tissue, this procedure was termed Descemet stripping automated endothelial keratoplasty (DSAEK).22 Facilitating donor tissue preparation by using a microkeratome enabled eye banks to provide precut donor tissue, making DSAEK rapidly accessible to corneal surgeons worldwide. Advantages of EK over PK included (1) better functional outcomes with faster visual recovery, (2) reduced risk of intraoperative bleeding or infections due to the surgery on a **closed globe** compared to the **open globe surgery** in PK, (3) elimination of suture-related complications with a preserved anterior corneal surface avoiding unpredictable postoperative refractive errors, (4) the lack of a large penetrating wound providing a tectonically stronger globe with reduced risk of traumatic wound dehiscence, and (5) reduced risk of allograft rejection.23,24 These advantages, together with the techniques’ high accessibility, played a key role in the remarkable increase of DSEK/DSAEK procedures over the following years and their implementation as the new gold standard for the treatment of endothelial pathologies. However, the DSEK/DSAEK techniques also had drawbacks, such as expensive donor tissue preparation and varying (suboptimal) visual acuity outcomes despite a technically successful surgery owing to thickness irregularities of the donor posterior stroma or stromal interface haze causing optical aberrations (► Fig. 2.2).25 Visual limitations owing to graft thickness irregularities were addressed by Busin et al when they introduced so-called ultrathin DSAEK grafts, which provided better clinical results than standard DSAEK but still required a costly microkeratome for graft preparation.26 Fig. 2.1 Schematic diagram of penetrating keratoplasty and the current endothelial keratoplasty techniques. (Reprinted from Melles GRJ, Dapena I. How to Get Started with Standardized ‘No-Touch’ Descemet Membrane Endothelial Keratoplasty (DMEK). Rotterdam, The Netherlands: Netherlands Institute for Innovative Ocular Surgery; 2014, with permission.) In 1998, Melles and colleagues had already presented the next refinement of EK. With this technique, called Descemet membrane endothelial keratoplasty (DMEK), a selective replacement of a Descemet membrane and its endothelium was achieved (► Fig. 2.2c).27 After the first DMEK surgeries, performed in 2006, it soon became evident that the near complete restoration of the corneal anatomy provided unprecedented visual outcomes10,28,29,30 and an even lower risk of allograft rejection.31,32 Furthermore, with DMEK, the anterior corneal lamella could still be used for deep anterior lamellar keratoplasty, also known as split cornea transplantation, permitting a more efficient use of donor tissue.33,34,35 Despite these advances, difficulties in tissue preparation, intracameral graft unfolding, and a relatively high incidence of postoperative graft detachments were perceived as the main obstacles for a widespread application of DMEK.36 Studeny et al attempted to facilitate intraoperative handling of the thin DMEK transplant by introducing DMEK-S, in which a graft consisting of only Descemet membrane and endothelium in the central optical portion, supported by a peripheral stromal rim, was manually dissected improving the graft’s stability inside the host anterior chamber.37 Later, Pereira et al and McCauley et al modified the concept of this technique by using a microkeratome for donor graft dissection, a technique popularized as Descemet membrane automated endothelial keratoplasty (DMAEK). In fact, DMEK-S/DMAEK provided better visual outcomes when compared with DSEK/DSAEK and were considered as technically less challenging than DMEK. However, a relatively high incidence of graft detachments often required a repeat air injection (rebubbling) to achieve graft adherence.38,39,40 In particular technique standardization and reproducibility of DMEK tissue preparation, provision of precut tissue, and standardization of intracameral DMEK graft unfolding solved many difficulties and helped corneal surgeons to take the first steps in DMEK or make the switch from DSEK/DSAEK to DMEK.41,42,43,44,45 With increasing experience also graft detachment rates could be reduced significantly as reported by different groups worldwide.46,47,48
2.1 Early Work
2.2 Endothelial Keratoplasty
2.3 Advantages
2.4 Drawbacks
2.5 Descemet Membrane Endothelial Keratoplasty
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